期刊
VIRUSES-BASEL
卷 13, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/v13050786
关键词
immunoassay; SARS-CoV-2 nucleocapsid protein; epitope coverage; quantitative antibody binding; protein microarray; SARS-CoV-2 antibodies; humoral response
类别
资金
- Hamad Medical Corporation [MRC-05-003]
- National Research Foundation, South Africa [64760]
- QBRI
The study demonstrated significant variations in the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral antigens within populations following natural infection, as shown through a novel protein microarray design.
The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population.
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